The major objective of this project is to elucidate the structure of the proteins of the lens and relate such information to the formation of cataract. A major hypothesis motivating this work is that the generation of molecular weight and insoluble protein is a cause of nuclear sclerosis and nuclear opacification. At present, a number of fundamental approaches are being pursued: 1. Continuation of the investigation of alpha crystallin which we believe is involved in the development of certain types of cataract. Our present studies directed at a better understanding of the interaction of the polypeptide chains comprising the alpha crystallin aggregates and of the effect of minor post translational chemical changes upon the aggregate state. This work has been stimulated by the observation that low molecular weight alpha crystallin is essentially absent in the nuclear region of older human lenses. 2. Elucidation of the structure of an 11,000 and 43,000 dalton polypeptide which represent a major fraction of the high molecular weight and insoluble components of the human lens and which are present in only small amounts in the low molecular weight soluble lens proteins. 3. Initiation of a search for non-sulfhydryl cross links in the insoluble protein. Such cross links may be another factor involved in the insolubilization of the lens proteins and may be a factor in the generation of cataract. 4. Examination of the conformation of alpha crystallin and high molecular protein from bovine lens. 5. Examination of the role of the sulfhydryl group and glutathione in maintaining the normal state of the lens proteins. 6. Investigation of the effect of calcium upon the aggregation of lens proteins. BIBLIOGRAPHIC REFERENCES: Chen, J.H., Lavers, G.C., and Spector, A.: Calf lens messenger ribonucleoprotein complexes: characterization and comparison of template activity with corresponding mRNAs. Biochim. Biophys. Acta 418, 39-51-1976. Dillon, J., Spector, A., and Nakanishi, K.: Identification of Beta-carbolines isolated from fluorescent human lens proteins. Nature 259, 422-423, 1976.